The Life Span Study (LSS) cohort of 94,000 survivors of the Hiroshima and Nagasaki atomic bombings is being studied in collaboration with the Radiation Effects Research Foundation (RERF). Cohort studies are used to quantify environmental radiation dose response and its dependence on histological subtype of tumor, age at exposure, sex, age at observation, time following exposure and other factors.<br;br>More than half a century after the atomic bombings, a statistically significant excess risk of cancer is still apparent. The latest LSS solid cancer incidence report published in 2007 updating the first comprehensive LSS cancer incidence report in 1994, includes 17,448 first primary cancers among the LSS survivors, of which 853 are estimated to be excess cases attributable to radiation exposure. The shape of the dose response for solid cancers as a group and for many individual cancer sites continues to be well described by a linear model. The most important finding is that the excess absolute rates for solid cancer increase throughout life for all ages. The excess relative risks associated with radiation exposure are high for cancers of the bladder cancer, breast cancer and lung cancer, whereas excess absolute rates are high for s of the stomach cancer, breast cancer, colon cancer and lung cancer. Solid cancer risks are especially high among these exposed in utero and early childhood. However, the uncertainty remains regarding the temporal patterns of the radiation-related cancer risk, especially among the survivor younger than 20 years of age at the time of the atomic bombings, and continued follow-up of this cohort is needed to clarify this uncertainty.<br;br>Among several new findings are the radiation-related excess risk of male breast cancer. Thyroid papillary microcarcinoma, a synergistic interaction between radiation and hepatitis C infection on liver cancer risk, an additive/multiplicative effects of radiation and smoking on lung cancer risk, and also an additive effect of ultraviolet and ionizing radiation exposures on basal cell skin cancer.<br;br>A multidisciplinary case-case approach is in progress to study genetic susceptibility to radiation-related breast cancer and ovarian cancer. This follows the previously reported phenomenon of extremely high, dose-specific relative risks for early-onset breast cancer (before age 35), which suggests increased sensitivity to radiation among a genetically predisposed population subgroup. In this study, early and late-onset breast cancer cases are compared and BRCA 1/2 and other candidate genes in breast cancer pathways are investigated using archived tissues. In another study using archived tissue materials, we estimated the prevalence of xeroderma pigmentasum (XP) heterozygosity to be about 1% in the Japanese population.<br;br>Construction of a database that incorporates all previous LSS mail survey data continues. This database will allow easy access to a large amount of information of epidemiological interest, i.e., tobacco use, alcohol intake, diet, reproductive history, occupations, medical history, and other factors.<br;br>